1-(6-Chloropyrimidin-4-yl)benzimidazole → HCID 134153731, compound

Participants

Reaction Conditions

Reaction Steps

TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (31.6 mg, 0.03 mmol) was added to (R)-5-((1-methylpyrrolidin-2-yl)methoxy)pyridin-2-amine (143 mg, 0.69 mmol), 1-(6-chloropyrimidin-4-yl)-1H-benzo[d]imidazole (159 mg, 0.69 mmol), sodium t-butoxide (99 mg, 1.03 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (59.8 mg, 0.10 mmol) in toluene (6 mL) at 20°C under nitrogen. The resulting suspension was stirred at 100 °C for 16 hours then cooled to room temperature. LCMS analysis indicates no SM, product peak present. The reaction mixture was concentrated _in vacuo_. The residue was dissolved in DCM (100 mL) and washed with water (100 mL). The organic layer was passed through phase separating cartridge and concentrated under reduced pressure. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in DCM. Pure fractions were evaporated to dryness to afford a yellow gum. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5µ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford (R)-6-(1H-benzo[d]imidazol-1-yl)-N-(5-((1-methylpyrrolidin-2-yl)methoxy)pyridin-2-yl)pyrimidin-4-amine (39.0 mg, 14.09 %) as an pale yellow solid. Experiment was re-opened on 08/06/2012 to record additional data for publication. 13C and HRMS data recorded as separate sections rather than within sample details due to ELN conflict when trying to sign and close with redundant project code.

Provenance & Evidence